A number of studies have indicated the existence of more than one type of benzodiazpine (BZ) receptor in brain [J. Parmacol. Exp. Ther., 221, 670 (1982), Pharmacol. Biochem. Behav., 11, 457 (1979), Pharmacol. Biochem. Behav., 10, 825 (1979), Nature, 286, 606 (1980), Nature, 286, 285 (1980), J. Parmacol. Exp. Ther., 212, 337 (1981)]. The evidence for this comes primarily from work with two classes of compounds: the triazolopyridazine and .beta.-carbolines. These drugs exhibit shallow inhibition curves in competing for .sup.3 H-flunitrazepam or .sup.3 H-diazepam binding sites in various brain regions and also show regional selectivity (being more potent in cerebellum than in cortex or hippocampus).
One benzodiazepine (7-chloro-1-(2,2,2-trifluorethyl)-5-(2-fluorophenyl)-1,3-dihydro-2H-1,4 benzodiazpeine-2-thione) known as quazepam has been reported to display a receptor binding profile similar to that of the triazolopyridazine and .beta.-carbolines described above [Life Sco., 35, 105 (1984), Neurosci. Lett., 38, 73 (1983)]. This compound displays a 54-fold difference in binding affinity for two BZ receptors (BZ-1 and BZ-2). A related benzodiazepine (7-chloro-1-(2,2,2-trifluorethyl)-5-(2-fluorophenyl)-1,3-dihydro-2H-1,4 benzodiazepine-2-one) known as 2-oxo-quazepam exhibited a 22-fold binding preference for the high affinity BZ receptor as well as an overall potency 14 times that of quazepam. In addition, 2-oxo-quazepam displays a much lower degree of non-specific binding (&lt;5 percent at 0.5 nM).
2-oxoquazepam's high affinity for BZ-1 receptors together with minimal non-specific binding at low concentrations is a novel feature that makes labeled forms of this compound ideally suited for identifying and detecting other compounds that have BZ-1 specific activity.